The cephalosporins are a well-known family of antibiotics that have gained wide-spread use in recent years in the treatment of pathogenic infections in mammals. A large number of cephalosporins have been prepared by varying the substituents at the 3- and 7-positions of the cephalosporin nucleus. However, the search still continues for compounds having high activity and a high degree of stability.
Although some newly-discovered cephalosporins have proven to be invaluable by virtue of their broad antibacterial spectrum against Gram-positive and Gram-negative bacteria, they do not appear to be effective against certain bacteria, e.g., Klebsiella pneumoniae, Proteus mirabillisci, Proteus vulgaris, Proteus morganii, and particularly Pseudomonas aeruginosa. These are noted as pathogens which cause serious infections in hospitals and clinics. One of the successful antibiotics against the above-mentioned bacteria is cephem having catechol moiety in 3-position. Japanese patent SHO-62-51688. SHO-62-148489, SHO-62-209082 and EP0269-298 disclose a cephalosporin compound of the formula ##STR1## This compound presents extremely high activity on MIC against gram negative bacteria, particularly against ps. aureginosa. However in vivo activity is lessened due to deactivation by COMT (catechol O-methyl transferase). During intensive study to circumvent the COMT-deactivation we found that the cephems having catechol substituted with halogen and/or nitro are resistent against COMT.